Summary~/8 T cells can be grouped into discrete subsets based upon their expression of T cell receptor (TCR) variable (V) region families, their tissue distribution, and their specificity. V~2 + T cells constitute the majority of~/8 T cells in peripheral blood whereas V81 + T cells reside preferentially in skin epithelium and in the intestine. ~/~ T cells are envisioned as first hne host defense mechanisms capable of providing a source of immune effector T cells and immunomodulating cytokines such as interleukin (IL) 4 or interferon (IFN) % We describe here the fine specificity of three distinct ~/~+ tumor-infiltrating lymphocytes (TIL) obtained from patients with primary or metastatic colorectal cancer, that could be readily expanded in vitro in the presence oflL-l~ and IL-7. Irrespective of donor, these individual ~/8 T cells exhibited a similar pattern of reactivity defined by recognition ofautologous and allogeneic colorectal cancer cells, renal cell cancer, pancreatic cancer, and a freshly isolated explant from human intestine as measured by cytolytic T cell responses and by IFN-~/release. In contrast, tumors of akemate histologies were not lysed, including lung cancer, squamous cell cancer, as well as the natural/lymphocyte-activated killer cell-sensitive hematopoietic cell lines T2, CIR, or Daudi. The cell hne K562 was only poorly lysed when compared with colorectal cancer targets. Target cell reactivity mediated by V8I + T cells was partially blocked with Abs directed against the TCR, the [32 or [37 integrin chains, or fibronectin receptor. Marker analysis using flow cytometry revealed that all three ~ T cell lines exhibit a similar phenotype. Analysis of the ~/8 TCR junctional suggested exclusive usage of the V81/D~3/J81 TCtk segments with extensive (~<29 bp) N/P region diversity. T cell recognition of target cells did not appear to be major histocompatibility complex restricted or to be correlated with target cell expression of heat-shock proteins. Based on the ability of some epithehal tumors, including colorectal, pancreatic, and renal cell cancers to effectively cold target inhibit the lysis of colorectal cancer cell lines by these V8I + T cell lines, we suggest that intestinal V~I + T cells are capable of recognizing cell surface Ag(s) shared by tumors of epithehal origin.
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